414P - Lessons learnt from clinico-genomic profiling of families with Li Fraumeni Syndrome: The largest case series from the Indian setting

Background

Li Fraumeni Syndrome (LFS) is an inherited cancer predisposition syndrome due to TP53 gene mutation. There is sparse literature on LFS from India owing to limited testing resources and less awareness among medical practitioners.

Methods

This is a retrospective study of patients and their family members presenting to the Medical Oncology department between April 2016 and October 2021, who were diagnosed with LFS at another hospital or at our centre.

Results

7 LFS families had 22 patients diagnosed (currently/historically) with malignancy, including 7 index cases and 15 1^st or 2^nd-degree relatives. Each family had median of 3 cancers (range 2-5); sarcoma (n=8, 36.3%) and breast cancer (n=5, 22.7%) being the commonest. 9 cancers occurred in the 7 index cases, including 2 cases with metachronous malignancies. Median age of the index cases at diagnosis was 22 years (range 9-63) with sarcoma as the commonest tumor in 5 (71.4%), of which leiomyosarcoma was the most frequent subtype (n=2, 28.5%). There were 8 TP53 mutation-positive cancer patients and 5 asymptomatic carriers. Remaining 14 family members with malignancy are not alive, hence are untested. Mutations were most commonly missense (n=5, 71.4%), most frequently at exon 5 (n=2, 28.5%), and the commonest aberration was replacement of arginine with histamine (n=3, 42.8%). All 7 families met the Classical and/or Chompret’s diagnostic criteria, including 3 (42.8%) that satisfied them even prior to onset of cancer in index cases. Yet, testing for LFS was done only in 2 (28.5%) families before presenting to us. 4 families are undergoing surveillance as per the Toronto protocol, while 2 families do not have living carriers for follow-up. 1 family dropped out after 1 year of surveillance due to the social and financial issues attached to a genetic cancer syndrome.

Conclusions

The diagnosis of LFS has socio-economic implications for patients and their family members, necessitating genetic counselling and early testing. Delay in genetic testing misses out the crucial window wherein asymptomatic carriers could be diagnosed and followed up. Mutation profiling of Indian LFS patients should also be done prospectively in the future to assess the uniqueness of LFS among Asians.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.